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Researchers Investigate
Immunity in Pigs

Producers want to safeguard their
investment by having the best pigs possible. They want healthy pigs that
recover quickly from infections without costly therapeutic drug treatments.
Consumers want safe pork products that contain less drug residues.

Some pigs are naturally healthier than
others. They seem to have heightened abilities to fight off infections. ARS
researchers are interested in finding out why some pigs in a population respond
better to infections. Identifying genes that endow resistance to each of the
large number of pathogen infections that impact swine is nearly impossible.
Instead of finding beneficial genes for each disease, it might be more useful
to find pigs that are better at fighting off pathogens in general.

When invaded by foreign agents, the immune
system responds to a complex array of antigens and initiates cell-mediated
responses, either type 1 immunity (responding to intracellular infections) or
type 2 immunity (responding to extracellular infections and allergens). The
type of response that dominates is the one best equipped to combat a particular
type of pathogen. Cells in the immune system communicate with each other
through hormone-like proteins called cytokines. Cytokines are secreted by cells
for each type of response and can suppress the activity of the other. So, the
way in which an immune system initially reacts to a pathogen is critical to a
pig's health.

Most health problems facing today's pigs
are respiratory in nature. USDA's Swine 2000 Survey states that 39.1
percent of deaths in grower/finisher pigs were due to respiratory diseases.
Indoor-reared pigs expressing type 1 immunity should be better suited to face
health challenges encountered in these production conditions, according to
immunogeneticist Joan Lunney, the research leader of ARS'
Immunology
and Disease Resistance Laboratory (IDRL) in Beltsville, Md.

In cell-mediated immunity, T cells
(lymphocytes) respond to invaders by binding to the surface of other cells that
display antigens. The cytokine interleukin-12 (IL-12) usually has the primary
role in enabling macrophages and T cells to attack invaders using type 1
immunity. IL-12 induces the expression of the cytokine interferon-gamma
(IFN-gamma), the main force behind the type 1 immune response. Therefore, a
high level of IFN-gamma in a pig after infection may be a good predictor that
the animal has developed a strong protective immune response against a virus,
although it may not be true for all viruses.

The development of protective immunity in
pigs is poorly understood. Gloria Solano-Aguilar, working in Lunney's lab,
recently showed that swine responses to IL-12 are lower than in cows. Unlike in
other animals, IL-12 does not cause high IFN-gamma responses in uninfected
swine. So, there must be other cytokine signals to induce an IFN-gamma
dominated response.

Because IL-12 seems to stimulate less of a
response in pigs, ARS scientists want to know how IFN-gamma is generated. They
want to define which genes control type 1 immune responses in pigs and how they
do it. A better understanding of the role that different types of immune
effector mechanisms have in mediating protective immunity against pig viral
diseases is key to developing effective vaccines.

What Makes A Pig Healthy?

In the coming years, Beltsville
researchers hope to find new cytokines and cytokine receptors and identify
several new genes, including ones that determine a type 1 response and others
that may prevent it. They are cooperating with other researchers to examine the
genetics and breeding results of pigs that respond well to IFN-gamma.

Their research has been aimed at defining
immune properties that result in pigs with improved production traits and
better abilities to respond to diseases and survive. They want to identify and
select pigs predisposed to develop a strong type 1 response to viral antigens
so they can develop genetic markers for this trait.

Harry Dawson and Joseph Urban of the
Nutrient
Requirements and Functions Laboratory (NRFL)--part of the
Beltsville Human Nutrition Research
Center--have led the effort to develop sensitive molecular tests for pig
cytokine genes and receptors predicted to be involved in both type 1 and type 2
immune responses. They have collaborated with IDRL researchers Lunney, Dante S.
Zarlenga, Ethiopia Beshah and Sandra Nishi to answer the question of which
pathogens cause one or the other type of gene expression profile.

Using these tests should also help them
identify genes that are believed to play a role in some pigs' ability to resist
infection with Toxoplasma gondii, a protozoan parasite that is present
in some pigs but usually causes little harm to them. T. gondii is more
of a food safety issue because it can cause birth defects when a pregnant woman
becomes infected. It can also cause serious problems in AIDS patients or others
with weakened immune systems. This team of swine researchers expects to
identify pig genes responsible for genetic differences in the ability among
pigs to prevent T. gondii from taking hold, and in doing that, identify
genes that stimulate type 1 immunity in general. This development would help
swine breeders also select for more viral disease-resistant stock.

Researchers at IDRL are collaborating with
Kelly M. Lager and Juergen Richt at the
National
Animal Disease Center (NADC) in Ames, Iowa, to examine a major pathogen
impacting pig production. They are looking at responses to respiratory
infections caused by swine influenza virus (SIV). They hope to apply their
results to Mycoplasma hyopneumoniae, the organism that triggers
mycoplasmal pneumonia. M. hyopneumoniae, SIV and porcine reproductive
respiratory syndrome virus (PRRSV) are associated with the porcine respiratory
distress complex (PRDC). Because pathogens are better able to overcome immune
defenses when they work in combination with each other, M. hyopneumoniae
can weaken the immune system and encourage secondary infections.

IDRL researchers want to determine how
genes develop strong type 1 immune response in pigs by looking at two different
viruses and comparing a weak type 1 immunity response to a strong one. With
their NADC collaborators, they will compare pigs infected with T. gondii
to pigs infected with SIV and PRRSV and examine their unique immune gene
expression profiles.

Lunney said a whole series of genes are
known to change expression during parasitic and viral infections. She said the
Beltsville team is interested in finding out if other pathogens stimulate
additional genes, besides those already known about. Additionally, the NRFL
scientists are developing the pig as an improved model for human nutrition
studies. Urban, Dawson and Solano-Aguilar (now at NRFL) plan to use these gene
expression assays to determine the effect of different nutrients on immune
functions.

Research Briefs

ARS' National Animal Germplasm
Program has officially added swine to its collection. This will help provide
breeders with the genetic tools
necessary to develop animals with disease resistance and other important
traits. Researchers have also started a national breed survey and developed
software to sample breeds. They are also working to improve germplasm
cryopreservation. Harvey Blackburn (970)
495-3268

Scientists are developing a
database known as the Feed Information
Technology (FIT) expert system. Through a cooperative agreement with
industry, ARS and their partners will identify, define and evaluate
relationships between a plant's growing conditions and its nutritional value.
The information collected on the chemical composition of forage could help
boost a herd's productivity. It could also help the environment by reducing
excess nutrients in livestock manure. David Mertens (608) 264-5288,
Richard Muck (608)
264-5245

A two-year cooperative study to
produce new vaccines for foot-and-mouth disease (FMD) recently began between
ARS and a veterinary institute in South Africa. The cooperating scientists are
using genetic engineering to
develop better
vaccines that respond to constant mutation by the FMD virus. Limiting the
presence of FMD overseas helps protect U.S. livestock.Plum Island Animal
Disease Center (631) 323-3202

ARS researchers and
collaborators developed a test to help
identify sexually
active mature sheep. Between 15 and 25 percent of all male sheep in the
United States may ignore ewe's mating overtures. The new test is based on the
premise that libido is closely linked to the ability to secrete testosterone.
Breeders prefer to let their flocks breed naturally and artificial insemination
involves high labor costs. John Stellflug (208) 374-5306

A
new test measures
the blood concentrations of a previously little-understood protein to evaluate
the health of poultry. Because ovotransferrin (OTF) increases in chickens with
infections, ARS researchers believe a better understanding of it, and other
acute phase proteins (APPs), could lead to new approaches for improving natural
disease resistance in poultry.Narayan Rath (479) 575-6189

An ARS researcher is
investigating nitrated
protein measurement as a biomarker of stress or injury. The naturally
occurring proteins may serve as an early warning system and identify an animal
recovering from an illness or potentially yielding unsafe meat or
milk.Ted Elsasser (301) 504-8281

A
new system
developed by an ARS scientist uses an electrostatic charge to trap airborne
dust that harbors Salmonella and other pathogenic bacteria. The system
sterilizes pathogens in poultry houses. It reduced Salmonella transmission and
other airborne pathogens by 80 to 95 percent in experimental and commercial
hatching cabinets. Bailey Mitchell (706) 546-3443